Original Article

Patterns of Antimicrobial Use in a Specialized Surgical Hospital in Southeast Nigeria: Need for a Standardized Protocol of Antimicrobial Use in the Tropics

Ugochukwu Uzodimma Nnadozie1,2, Chukwuma David Umeokonkwo3, Charles Chidiebele Maduba1, Ifeanyichukwu I. Onah4, Dorothy Igwe‑Okomiso3, Iheuko S. Ogbonnaya4, Cosmas Kenan Onah3, Patric Chukwuemeka Okoye4, Ann Versporten5, Herman Goossens5 1Division of Plastic , Department of Surgery, Alex Ekwueme Federal University Teaching Hospital, 2Department of Surgery, College of Health Sciences, Ebonyi State University, 3Department of Community , Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, 4Department of , National Orthopaedic Hospital, Enugu, Nigeria, 5Laboratory of , Faculty of Medicine and Health Science, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium

Abstract

Background: remains a growing global health menace. One of the key actions to curb this menace by the World Health Organization is antimicrobial stewardship (AMS). A prescription protocol is one of the cost‑effective AMS interventions in surgery. This study determines the patterns of antimicrobial usage in a hospital specialized in orthopedic and plastic care in Nigeria. Methods: A cross‑sectional survey was carried out at National Orthopaedic Hospital Enugu, a tertiary hospital specialized in orthopedic and plastic surgeries in Southeast Nigeria in May 2019. All the inpatients were included in the study. A standardized tool for point prevalence survey was used to collect data. Data were analyzed using Epi Info version 7.2.4. Results: A total of 127 inpatients participated in the survey with 387 antimicrobial encounters. The most common reasons for antimicrobial use were for the treatment of community‑acquired infections (65.0%) and prophylaxis (29.4%). The decision for their use was made majorly on an empirical basis (92.4%). The reasons for antimicrobial prescriptions were documented in the majority (97.5%) of the cases and stop review dates in all (100%) of the prescriptions. Ceftriaxone (25.7%), tinidazole (21.9%), and metronidazole (14.6%) were the commonest antimicrobials prescribed among the patients. Conclusion: Orthopedic and plastic surgery practices require tailored prophylactic regimens in the tropics due to peculiarities of both the specialties and the subregion. The claim that existing protocols in the temperate regions may apply in the tropics has been questioned due to the microbial profile on the tropics.

Keywords: Antimicrobial protocol in surgery, antimicrobial resistance, antimicrobial stewardship, prophylactic

Introduction AMS programs are known to improve antimicrobial use, patient outcomes, lower the risk of developing resistance, Antimicrobial resistance (AMR) is recognized globally as lower the rate of health-care-associated infections, and a threat to .[1] This is due to the ageless battle reduce the cost of treatments among others.[3,4] AMS, against microbes, especially bacteria which has increasingly infection prevention and control, and patient safety are the led to resistance to almost all antimicrobials available. Global and national policy initiatives have acknowledged Address for correspondence: Dr. Ugochukwu Uzodimma Nnadozie, that excessive and inappropriate antimicrobials use are Division of Plastic Surgery, Department of Surgery, Alex Ekwueme major contributors to antibiotic resistance, and that there is a Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria. need to improve the antimicrobial use through antimicrobial E‑mail: [email protected] stewardship (AMS).[1] AMS is a group of interventions aimed at improving antibiotic use. It is an important part of efforts This is an open access journal, and articles are distributed under the terms of the Creative to control antibiotic resistance according to the World Health Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit [2] Organization. is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] Access this article online Quick Response Code: How to cite this article: Nnadozie UU, Umeokonkwo CD, Maduba CC, Website: Onah II, Igwe-Okomiso D, Ogbonnaya IS, et al. Patterns of antimicrobial www.njmonline.org use in a specialized surgical hospital in Southeast Nigeria: Need for a standardized protocol of antimicrobial use in the tropics. Niger J Med 2021;30:187-91. DOI: 10.4103/NJM.NJM_225_20 Submitted: 19‑Dec‑2020 Revised: 01‑Feb‑2021 Accepted: 26-Feb-2021 Published: 22-Apr-2021

© 2021 Nigerian Journal of Medicine | Published by Wolters Kluwer - Medknow 187 Nnadozie, et al.: Patterns of antimicrobial use in surgery three pillars of an integrated approach to health systems antimicrobial point prevalence to collect information from the strengthening.[5] patients’ hospital records. Patients’ demographics, laboratory use, antimicrobial indications, stop review date, and reasons Stewardship interventions can be structural, persuasive, for antimicrobial use were collected. Malaria is endemic in the enabling, or restrictive. In structural intervention, a new study area and accounted for the inclusion of antimalarials in diagnostic test could be introduced to guide antibiotic use. The the antimicrobial spectrum (antimalarials are not necessarily use of prescription audit and feedback is a form of persuasive antibiotics). AMS, whereas providing education to the prescribers on the appropriate use of antimicrobial could be seen as enabling. Data analysis In some cases, a restrictive approach could be used where Data collected with the standardized tool developed the some agents are reserved and used only within well‑defined University of Antwerp “https://www.global‑pps.com,” was conditions.[3] A combination of these interventions can make analyzed using Epi Info version 7.2.4 Frequencies were up a hospital antimicrobial/antibiotic stewardship. calculated and results presented in tables and chart. A recent systematic review of antimicrobial use and AMS shows a lack of adequate data and studies from sub‑Saharan Results [6] Africa, especially Nigeria. This study aims to survey the A total of 127 inpatients participated in the survey, patterns of antimicrobial use in a tertiary Orthopaedic and and of these, 120 were admitted in the adult surgical Plastic Surgery hospital in Southeast Nigeria. The study ward, six in the pediatric surgical ward, and one in the will form the basis for prioritizing AMS hospital programs adult intensive care unit. A total of 106 (83.5%) of the that will help curb the AMR menace, especially in low‑ and participants were on one antimicrobial or the other during middle‑income countries. the survey. Ninety‑six (90.6%) inpatients were above 18 years of age. Seventy‑two (67.9%) patients were males, Methods and the most common age groups were 25–34 years, Ethical consideration then >50 years categories [Table 1]. There were a total of 357 antimicrobial encounters. The maximum number Ethical approval was obtained from the Institutional Review of antimicrobials a patient was receiving was eight Board of National Orthopaedic Hospital Enugu (NOHE). (median: 4; interquartile range: 3, 5). Study area The most common reasons for antimicrobial use were for This study was carried out in NOHE. This is one of the three the treatment of community‑acquired infections (65.0%) as government orthopedic hospitals in Nigeria. It is situated in against hospital‑acquired (nosocomial) infections (5.3%)] Enugu State and strategically located to serve Nigerians residing and for prophylaxis (29.4%) [Table 1], and the decision for in the Eastern and Southern flanks of the country. It is a 240‑bed their use was made majorly on an empirical basis (92.4%) as specialist hospital providing orthopedic, trauma, and plastic against targeted antimicrobial prescription (7.6%) [Table 2]. surgery services. It has a regional trauma/burns Center and a The reason for antimicrobial prescriptions was documented comprehensive laboratory. Five full‑time consultant plastic in the majority (97.5%) of the cases and stop review dates in surgeons run three units and 14 orthopedic surgeons run six all (100%) of the prescriptions. orthopedic units. There are sixty residents (trainee surgeons), 15 consulting clinics running Monday to Friday. The hospital operates five theaters, one dedicated to orthopedics, one to plastic Table 1: Sociodemographic characteristic of the patients surgery, both specialties share the trauma, septic, and general and reasons for antimicrobial use theaters. The hospital does not have a written antibiotic guideline. Variable Frequency (%) Routinely, patients presenting with open fractures/wounds are Age (years) put on cephalosporins and imidazoles though not a written <18 10 (9.4) policy. Patients with open fractures are seen by both orthopedic 18-24 11 (10.4) and plastic teams in their emergency rooms. 25-34 27 (25.5) 35-44 19 (17.9) The bed occupancy rate on the day of the survey was 45-54 12 (11.3) 52.9% (127/240). >55 27 (25.5) Study design and population Sex Male 72 (67.9) A cross‑sectional survey of all the inpatients in the wards in Female 34 (32.1) May 2019 was carried out. Inpatients in the wards at 08:00 h Reasons for antimicrobial use of the survey day were included. Community acquired infection 232 (65.0) Study instruments Hospital acquired infection 19 (5.3) We used the standardized tool developed by the University Prophylaxis 105 (29.4) of Antwerp “https://www.global‑pps.com” for assessing Unknown 1 (0.3)

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The duration of prophylactic antibiotic usage was more than Discussion 24 h in 101 (96%) of the patients on prophylaxis. Two patients The antimicrobial use in orthopedic and plastic surgeries is (2%) had prophylaxis for 24 h and the remaining 2% had it often more aggressive than in other fields of surgery because for <24 h too. the consequences of infections can be disastrous. Bone The common antimicrobial use by indications is portrayed infection is considered the most dreaded complication of in Table 3. Table 4 and Figure 1 show the diagnoses, for .[7] The point prevalence of antimicrobial which antimicrobials were used, and the antibiotics that use, though high (83.5%) is similar to what obtains in the were commonly prescribed in the study hospital. The subregion.[8,9] The use of antibiotics for prophylaxis is also most common antimicrobials prescribed for treatment slightly favored toward prolonged duration. There is a were ceftriaxone (26.3%), tinidazole (22.0%), and varied range of practices in the duration of administration of metronidazole (15.5%) for community‑acquired infections; prophylactic antimicrobials, ranging from a single dose to as ceftriaxone (28.6%), tinidazole (23.8%), and metronidazole much as 14 days postoperatively.[10] This pattern varies with (15.2%) for prophylaxis and artemether/lumefantrine (31.6%), the findings in tertiary hospitals that covered more than just artemether (15.8%), and tinidazole for hospital‑acquired surgical cases,[11] where their point prevalence of antimicrobial infections, respectively. use was much lower (44%). We observed a high level of the antimicrobial prescriptions were Table 2: Antimicrobial prescription quality indicators given empirically (92.4%) and mainly for community‑acquired Variable Frequency (%) infections. The most common diagnosis was soft tissue, and Treatment skin infections followed by bone and joint infections. This Empirical 330 (92.4) may be explained by the fact that the hospital is dedicated Targeted 27 (7.6) mainly to plastic and orthopedic surgeries. The use of empirical Reason in note antibiotics in patients with burn injuries and other soft‑tissue Yes 348 (97.5) trauma stems mainly from the fear of overwhelming infection. No 9 (2.5) Owing to poor transport and emergency services, patients Guideline compliance are most likely to present outside the golden hour and with Yes 19 (5.3) contamination of the wounds.[12] Besides, the lack of adequate No 1 (0.3) spacing and ward design make breaks in the aseptic techniques NA 337 (94.4) more likely, encouraging the to lean on antibiotics. Stop review date documentation Other infections noted in the study can be explained as Yes 357 (100.0) nosocomial infections. They were relatively low occurrences. No 0 Route of administration Sepsis and upper respiratory tract infection are known Oral 129 (36.1) complications of surgical patients acquired as nosocomial Parenteral 228 (63.9) infections. Few other nosocomial infections (urinary tract, NA: Not applicable pneumonia, and gastrointestinal infections) were observed. The choice of antibiotics for their treatment commonly falls within Table 3: Common antimicrobial use by indication Amoxicillin and 3.6 Variable Frequency (%) enzyme inhibitor Community acquired infection Ceftriazone 61 (26.3) Gentamicin 3.9 Tinidazole 51 (22.0) Metronidazole 36 (15.5) Levofloxacine 5.6 Cefuroxime 19 (8.2) Levofloxacin 14 (6.0) Cefuroxime 7.0 Hospital acquired infection Artemether and lumefanterine 6 (31.6) Metronidazole 14.6 Artemether 3 (15.8) Tinidazole 2 (10.5) Amoxicilling and enzyme inhibitor 1 (5.3) Tinidazole 21.9 Prophylaxis Ceftriaxone 30 (28.6) Ceftriaxone 25.7 Tinidazole 25 (23.8) Metronidazole 16 (15.2) 0.05.0 10.0 15.0 20.0 25.0 30.0 Cefuroxime 6 (5.7) Percentage Gentamicin 6 (5.7) Figure 1: The most common antimicrobials prescribed among the patients

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the center as other centers in the country and other countries Table 4: Ten most common diagnoses treated with in the subregion give it beyond 24 h.[9,14] A reason adduced therapeutic antimicrobial for this was that tropical region being hot and humid support Diagnosis n (%) bacterial colonization of both wounds and fomites.[7] Our Skin/soft tissue infection 49 (52.1) study center being a tropical hospital may have imbibed this Bone and joint infection 19 (20.2) age‑long practice from anecdotal observations. This practice Malaria 17 (18.1) is riddled with lots of controversies with some insisting that Sepsis 3 (3.2) a clean theater is all that is necessary to prevent infection URTI 2 (2.1) and others positing that even an ultra‑clean theater does not Cystitis 1 (1.1) suffice, especially where an implant is used.[10,15] In orthopedic GI infection 1 (1.1) and plastic surgeries, the use of implants is very common. HIV 1 (1.1) This might have been responsible for the protracted antibiotic Pneumonia 1 (1.1) URTI: Upper respiratory tract infection, GI: Gastrointestinal prophylaxis in the survey. In a multicenter study involving three tertiary hospitals in northern Nigeria, only 22.5% of the [16] the available local antimicrobials that are also used in plastic antibiotics prescriptions were made for surgical prophylaxis. and orthopedic practices. Malaria is endemic in the study area. This is slightly lower than the prophylactic antibiotics observed It was the third most common diagnosis and accounted for in this specialized plastic and orthopedic center. This difference the inclusion of antimalarials in the antimicrobial spectrum. in prophylactic antibiotics prescription may be related to the peculiarities in orthopedics and plastic surgeries. It could also Antimicrobial Prescription Quality indicators: There was be related to the use of the presumptive antibiotics which is commendable documentation of reasons for prescriptions commonly employed in trauma, especially in settings of open (97.5%) and stop review date (100%). These findings have fractures.[9,17] been found in some studies in the same region.[8,9] These should be sustained as it portrays good AMS. However, the It is, therefore, necessary to develop a prophylactic guideline majority (92.4%) of the prescriptions were empirical with that is tailored to orthopedics and plastic surgeries in this the most used for prophylaxis. This portrays a very low setting. Such guidelines would be able to address the peculiar level (7.6%) of targeted antimicrobial use, in the study area, microbial profile of the tropics and the sensitive nature and calls for an urgent need for improved AMS to avoid the of plastic/orthopedic practice in this subregion. Extended disaster of AMR in this specialized hospital. This finding did prophylactic antibiotics have been suggested to be sustained [7] not differ from the report in other bigger tertiary hospitals in till epithelial tissue covers the surgical wound. Even in the Africa with more clinical than just surgery.[8,11,13] temperate regions, variations have been observed in the pattern of organisms encountered and antibiotics used.[18] Each region Third‑generation cephalosporin (Ceftriaxone) was the most or subregion should undertake the responsibility of developing prescribed antimicrobial, followed by the imidazoles (tinidazole a specialty‑based region‑specific guidelines on prophylaxis. and metronidazole), then the second‑generation The traditional teaching has been to resort to broad‑based cephalosporin (cefuroxime). The use of quinolones, antibiotics. This does not take into cognizance of the fact that aminoglycosides, and ampicillins were less pronounced. The broad‑spectrum antibiotics lead to resistance which is a feared choice of antimicrobial was not based on any guidelines. complication of antibiotics abuse.[19] Availability, best guess, and cost must have contributed significantly to their choices, as prescription based on antibiotic The experience of surgeons in the subregion may have sensitivity was not the common practice noted in the study. informed the perceived unwillingness to adopt the traditional [20] The antimicrobials were used mostly for surgical prophylaxis prophylactic regimen. Despite the knowledge of the and community‑acquired infections. The prophylactic use may traditional concept, extended use of antibiotics to an average of have contributed to the high parenteral route of administration about seven days has been common.[21] A case for presumptive observed as this is usually given or commenced at the induction antimicrobial use has been made in the region.[9] This can cover of anesthesia. These findings are similar to what had been for trauma cases, the same cannot be said for an implant, and reported in earlier studies,[8,9,11] even though these studies aesthetic surgery cases. A review of this practice viz‑a‑viz a involved other specialties in medical practice. The need for a comparison with the conventional <24 h regimen is necessary. review of antimicrobial use, to improve AMS while sustaining This survey captured patients who were on prophylactic, some prescription quality indicators, is very overt in our study. presumptive as well as therapeutic antimicrobial use. This is much more important in plastic and orthopedic surgery Therefore, there is a need to develop a standardized guideline practices where AMR may be very disastrous, especially in in the subregion for orthopedic, plastic, and implant surgeries. antimicrobial use. We also observed that as much as 96% of patients receiving Limitations prophylactic antibiotics had it beyond 24 h. This practice of This was a single‑center study. We did not assess the giving prophylactic antibiotics beyond 24 h is not limited to peculiarities of implant versus nonimplant procedures.

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onclusion doi:10.4103/0019-5413.159556. C 8. Umeokonkwo CD, Madubueze UC, Onah CK, Okedo-Alex IN, Adeke AS, Orthopedic and plastic surgical practices require tailored Versporten A, et al. Point prevalence survey of antimicrobial prescription antimicrobial protocol in the tropics due to peculiarities of both in a tertiary hospital in South East Nigeria: A call for improved antibiotic stewardship. J Glob Antimicrob Resist 2019;17:291-5. doi: 10.1016/j. subspecialties and the subregion. While this is still awaited, jgar.2019.01.013. Epub 2019 Jan 19. PMID: 30668994. the practice of extended antibiotic prophylaxis remains the 9. Nnadozie UU, Umeokonkwo CD, Maduba CC, Igwe-Okomiso D, practice guided by fear of disaster from infections. The claims OnahCK, Madubueze UC, et al. Antibiotic use among surgical that existing protocols in the temperate regions may apply in inpatients at a tertiary health facility: A case for a standardized protocol the tropics have been questioned due to the microbial profile on for presumptive antimicrobial in the developing world. Infect Prev Pract 2020;2:100078. Available from: https://doi.org/10.1016/j. the tropics. This, therefore, necessitates a tailored guideline for infpip.2020.100078. antimicrobial use in the tropical subregion, especially for some 10. Yeap JS, Li1n JW, Vergis M, Yenng A, Chin CK, Singh H. Prophylactic surgical subspecialties such as plastic and orthopedic surgeries. antibiotics in orthopaedic surgery: Guidelines and practice. Med J Malaysia 2006;61:181-8. Acknowledgment 11. Horumpende PG, Mshana SE, Mouw EF, Mmbaga BT, Chilongola JO, We acknowledge the University of Antwerp for allowing us de Mast Q. Point prevalence survey of antimicrobial use in three hospitals in North-Eastern Tanzania. Antimicrob Resist Infect Control use their Global Point Prevalence Survey platform. 2020;9:149. 12. Onah II, Orji MO. Presentation and intervention time for plastic surgical Financial support and sponsorship patients presenting at the trauma unit, National Orthopaedic Hospital, Nil. Enugu. Niger J Plast Surg 2008;2:6-10. 13. Fowotade A, Fasuyi T, Aigbovo O, Versporten A, Adekanmbi O, Conflicts of interest Akinyemi O, et al. Point prevalence survey of antimicrobial prescribing There are no conflicts of interest. in a Nigerian hospital: Findings and implications on antimicrobial resistance. West Afr J Med 2020;37:216-20. 14. Labi AK, Obeng-Nkrumah N, Nartey ET, Bjerrum S, Adu-Aryee NA, References Ofori-Adjei YA, et al. Antibiotic use in a tertiary healthcare facility in 1. Allcock S, Young EH, Holmes M, Gurdasani D, Dougan G, Sandhu MS, Ghana: A point prevalence survey. Antimicrob Resist Infect Control et al. Erratum: Antimicrobial resistance in human populations: 2018;7:15. 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